DNA Oligonucleotide 3′-Phosphorylation by a DNA Enzyme

Camden, Alison J.; Walsh, Shannon M.; Suk, Sarah H.; Silverman, Scott

doi:10.1021/acs.biochem.6b00151

Cited by 32 publications

(25 citation statements)

References 54 publications

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“…Nucleic acid sequence space is densely populated with RNA and DNA molecules that catalyze phosphoryl or thiophosphoryl group transfer ( 2 , 7 – 14 ). All characterized kinase ribozymes and deoxyribozymes promote O- phosphorylation of a polynucleotide 5΄OH, 3΄OH or 2΄OH moiety ( 1 , 2 , 15 , 16 ). Kinase ribozymes could have supported complex small-molecule metabolism during an RNA world by promoting phosphorylation of numerous other molecules, although the potential of ribozymes to utilize alternative phosphoryl acceptors remains largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Nucleobase modification by an RNA enzyme

Poudyal

Nguyen

Lokugamage

et al. 2016

Nucleic Acids Research

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Ribozymes can catalyze phosphoryl or nucleotidyl transfer onto ribose hydroxyls of RNA chains. We report a single ribozyme that performs both reactions, with a nucleobase serving as initial acceptor moiety. This unprecedented combined reaction was revealed while investigating potential contributions of ribose hydroxyls to catalysis by kinase ribozyme K28. For a 58nt, cis-acting form of K28, each nucleotide could be replaced with the corresponding 2΄F analog without loss of activity, indicating that no particular 2΄OH is specifically required. Reactivities of two-stranded K28 variants with oligodeoxynucleotide acceptor strands devoid of any 2΄OH moieties implicate modification on an internal guanosine N-2, rather than a ribose hydroxyl. Product mass suggests formation of a GDP(S) adduct along with a second thiophosphorylation, implying that the ribozyme catalyzes both phosphoryl and nucleotidyl transfers. This is further supported by transfer of radiolabels into product from both α and γ phosphates of donor molecules. Furthermore, periodate reactivity of the final product signifies acquisition of a ribose sugar with an intact 2΄-3΄ vicinal diol. Neither nucleobase modification nor nucleotidyl transfer has previously been reported for a kinase ribozyme, making this a first-in-class ribozyme. Base-modifying ribozymes may have played important roles in early RNA world evolution by enhancing nucleic acid functions.

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Section: Introductionmentioning

confidence: 99%

Nucleobase modification by an RNA enzyme

Poudyal

Nguyen

Lokugamage

et al. 2016

Nucleic Acids Research

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“…The DNAzymes present in the database are classified according to the reaction that they catalyze, namely: RNA cleavage ( 1 , 7 ), DNA cleavage ( 9 , 22 ), RNA ligation ( 6 , 23–25 ), DNA ligation ( 24 , 26 ), DNA site-specific depurination ( 27 ), Porphyrin metalation ( 28 , 29 ), DNA phosphorylation ( 30 , 31 ), DNA capping ( 32 ), amino acid side-chain modification ( 9 , 33 , 34 ), thymine dimer repair ( 35 , 36 ), Copper-mediated Azide-Alkyne Cycloaddition (CuAAC) ( 37 ), Dephosphorylation ( 38 ), Diels-Alder ( 39 ), Tyrosine azido‐adenylylation ( 40 ), Modification of Phosphorylated Amino Acid Side Chains ( 41 , 42 ), Tyrosine Phosphorylation ( 43 , 44 ), Glycosylation ( 45 ), Reductive amination ( 46 ), Amide hydrolysis ( 47 , 48 ), and Ester hydrolysis ( 48 ). This classification allows users to apply filters while browsing the DNAzymes page, which can be accessed from the toolbar and from the quick links on the Home page.…”

Section: Database Contentmentioning

confidence: 99%

DNAmoreDB, a database of DNAzymes

Ponce-Salvatierra

Boccaletto

Bujnicki

2020

Nucleic Acids Research

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Deoxyribozymes, DNA enzymes or simply DNAzymes are single-stranded oligo-deoxyribonucleotide molecules that, like proteins and ribozymes, possess the ability to perform catalysis. Although DNAzymes have not yet been found in living organisms, they have been isolated in the laboratory through in vitro selection. The selected DNAzyme sequences have the ability to catalyze a broad range of chemical reactions, utilizing DNA, RNA, peptides or small organic compounds as substrates. DNAmoreDB is a comprehensive database resource for DNAzymes that collects and organizes the following types of information: sequences, conditions of the selection procedure, catalyzed reactions, kinetic parameters, substrates, cofactors, structural information whenever available, and literature references. Currently, DNAmoreDB contains information about DNAzymes that catalyze 20 different reactions. We included a submission form for new data, a REST-based API system that allows users to retrieve the database contents in a machine-readable format, and keyword and BLASTN search features. The database is publicly available at https://www.genesilico.pl/DNAmoreDB/.

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“…DNAzyme-catalyzed reactions constitute a new area of biological research. Despite the fact that there are only four nucleobases, DNAzymes can facilitate a wide range of reactions (Boxes 2 and 3), including cleavage and ligation of DNA or RNA [57,58], RNA branching [59], synthesis of nucleopeptide bonds [60], phosphorylation [61], depurination, adenylation, and porphyrin metallation of DNA [6,62] (Figure 4). These reactions further helped in understanding the potential of DNA as a catalytic molecule.…”

Section: Dnazyme-catalyzed Reactionsmentioning

confidence: 99%

Advanced Selection Methodologies for DNAzymes in Sensing and Healthcare Applications

Kumar

Jain

Dilbaghi

et al. 2019

Trends in Biochemical Sciences

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DNAzymes have been widely explored owing to their excellent catalytic activity in a broad range of applications, notably in sensing and biomedical devices. These newly discovered applications have built high hopes for designing novel catalytic DNAzymes. However, the selection of efficient DNAzymes is a challenging process but one that is of crucial importance. Initially, systemic evolution of ligands by exponential enrichment (SELEX) was a labor-intensive and time-consuming process, but recent advances have accelerated the automated generation of DNAzyme molecules. This review summarizes recent advances in SELEX that improve the affinity and specificity of DNAzymes. The thriving generation of new DNAzymes is expected to open the door to several healthcare applications. Therefore, a significant portion of this review is dedicated to various biological applications of DNAzymes, such as sensing, therapeutics, and nanodevices. In addition, discussion is further extended to the barriers encountered for the real-life application of these DNAzymes to provide a foundation for future research. Glossary Chromatography: a technique used for the physical separation of mixtures into their components. All forms of chromatography work on the same principle, in that, all have a stationary phase and a mobile phase. The approach is wellknown for its high sensitivity because of competitive interaction between the desired molecule and target immobilized stationary phase that are mainly composed of agarose beads. Combinatorial chemistry: synthetic method used to prepare a library of structurally related analogues in a single process. Currently, vast ranges of simulation software are used for generating combinatorial library. Electrochemical detection: the basic principle of electrochemical biosensors involves immobilization of selected functional DNA molecules on an electrode surface that specifically bind to a ligand, which can further lead to a change in the current or voltage. Electrophoresis: analysis technique used to efficiently separate charged particles from each another based on differences in their mobility. It can be used to separate a variety of small and large target molecules. The major shortcoming associated is that the target molecule should have a sufficient size to induce mobility changes. G-quadruplex DNAzyme: single-stranded G-rich aptamer sequences spontaneously form an intramolecular four-stranded helical structure (G4). Associates with the hemin group to form the catalytic G4-hemin-DNAzyme complex. This complex DNAzyme catalyzes the oxidation reaction of hydrogen peroxide to result in the generation of chemiluminescence. Logic gate: a logic gate performs a logical operation (Boolean algebra) on given inputs in order to generate a single electrical output. Different logic gates are combined using combinatorial or sequential approaches for computer programming. Basic logic gate series include-AND, OR, NOT, XOR, NOR, NAND, and XNOR.

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DNA Oligonucleotide 3′-Phosphorylation by a DNA Enzyme

Cited by 32 publications

References 54 publications

Nucleobase modification by an RNA enzyme

Nucleobase modification by an RNA enzyme

DNAmoreDB, a database of DNAzymes

Advanced Selection Methodologies for DNAzymes in Sensing and Healthcare Applications

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